PROJECT SUMMARY The human papillomavirus (HPV) vaccine offers the unprecedented opportunity to prevent nearly all cervical and anal cancers and a high proportion of vaginal, oropharyngeal, vulvar and penile cancers, where HPV is the etiologic agent. HPV vaccination is recommended for all children ages 11-12, with catch up for females to age 26 and males to age 21. However, despite clear and indisputable value in cancer prevention, uptake and completion of the HPV vaccine series has lagged far behind the goal of 80%. Provider recommendation is the strongest determinant of HPV vaccination, but slow translation of guidelines for preventive services, such as immunizations, into practice is a known challenge. Practice Facilitation (PF) is a multicomponent quality improvement intervention approach that has well-established efficacy, in which external support and resources are provided to build the internal capacity of practices to improve quality of care and patient outcomes. Our central goal is to identify the optimal approach to implementing an evidence-based intervention for the uptake and completion of HPV vaccine among adolescents receiving care in the community, guided by implementation science theory. AIM 1: Determine the clinical effectiveness and cost-effectiveness of two modalities for delivering a multi-component PF intervention to increase HPV vaccination initiation and completion in community-based pediatric practices. We will compare the traditional in-person Coach PF modality to a lower-resource Web-Based PF modality. The primary patient outcome is HPV vaccination. We will also examine and compare the sustainability of practice changes on vaccination rates and the effects over time for each intervention modality. H1: Both interventions will result in significant increases in HPV vaccination from baseline over time. H2: Increases in the rate of HPV vaccination will be higher and sustained for a longer period of time in the Coach PF Arm as compared with the Web-Based PF Arm. H3: The Web-Based PF Arm will be more cost-effective than the Coach PF Arm. AIM 2. Understand mechanisms of why the PF intervention may work better for some pediatric practices than others for HPV vaccination. We will examine theory-based determinants at the organizational, provider, and patient levels that may mediate (explain) or moderate (change) the effects of the PF intervention on vaccination outcomes. H4: Adoption of changes (process variables) and patient factors will mediate effects of the intervention on HPV vaccination outcomes. H5: Organizational factors, provider attitudes, and intervention characteristics will moderate intervention effects on HPV vaccination outcomes. The findings will inform organizations about which PF modality to use among their constituent practices to improve HPV vaccination rates, with potential for future national dissemination.